rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2010-4-26
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pubmed:abstractText |
BACKGROUND: Previous work has shown reduced expression levels of let-7 in lung tumors. But little is known about the expression or mechanisms of let-7a in prostate cancer. In this study, we used in vitro and in vivo approaches to investigate whether E2F2 and CCND2 are direct targets of let-7a, and if let-7a acts as a tumor suppressor in prostate cancer by down-regulating E2F2 and CCND2. METHODOLOGY/PRINCIPAL: Findings Real-time RT-PCR demonstrated that decreased levels of let-7a are present in resected prostate cancer samples and prostate cancer cell lines. Cellular proliferation was inhibited in PC3 cells and LNCaP cells after transfection with let-7a. Cell cycle analysis showed that let-7a induced cell cycle arrest at the G1/S phase. A dual-luciferase reporter assay demonstrated that the 3'UTR of E2F2 and CCND2 were directly bound to let-7a and western blotting analysis further indicated that let-7a down-regulated the expression of E2F2 and CCND2. Our xenograft models of prostate cancer confirmed the capability of let-7a to inhibit prostate tumor development in vivo. CONCLUSIONS/SIGNIFICANCE: These findings help to unravel the anti-proliferative mechanisms of let-7a in prostate cancer. Let-7a may also be novel therapeutic candidate for prostate cancer given its ability to induce cell-cycle arrest and inhibit cell growth, especially in hormone-refractory prostate cancer.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20418948-10666388,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20418948-10706289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20418948-10773440,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20418948-15659339,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20418948-15838517,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20418948-19074899
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
1932-6203
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
5
|
pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
e10147
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pubmed:meshHeading |
pubmed-meshheading:20418948-Cell Cycle,
pubmed-meshheading:20418948-Cell Line, Tumor,
pubmed-meshheading:20418948-Cell Proliferation,
pubmed-meshheading:20418948-Cyclin D2,
pubmed-meshheading:20418948-Down-Regulation,
pubmed-meshheading:20418948-E2F2 Transcription Factor,
pubmed-meshheading:20418948-Humans,
pubmed-meshheading:20418948-Male,
pubmed-meshheading:20418948-MicroRNAs,
pubmed-meshheading:20418948-Prostatic Neoplasms,
pubmed-meshheading:20418948-Transfection
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pubmed:year |
2010
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pubmed:articleTitle |
MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2.
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pubmed:affiliation |
Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. dongqc168@yahoo.com.cn
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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